Controlled-release drug delivery systems, particularly sustained-release preparations, are advantageous in that they help to reduce the frequency of administration of a drug without detracting from the effect of medication, prevent any sudden elevation of the blood concentration of the drug to reduce the risk of side effects, and maintain a therapeutically effective blood concentration for an extended period of time. Therefore, much research has been undertaken in the field of controlled release technology from the aspects of active drug, formulation and dosage form. By way of illustration, there are known an encapsulated preparation such that a core containing an active ingredient is covered with a shell, and a matrix type preparation such that an active ingredient has been dispersed in a release-controlling layer. These preparations are generally provided in such dosage forms as tablets, capsules and granules.
Meanwhile, many drug substances are absorbed mostly from the small intestine and, to a lesser extent, from the large intestine. Moreover, in humans, reportedly it takes about 5 to 6 hours for an orally administered drug to reach the large intestine.
However, in oral administration, the residence time of the drug in the digestive canal is of necessity limited even if its release is critically controlled by a sophisticated controlled release system, so that the drug is not efficiently absorbed but is excreted from the body without being fully utilized. Furthermore, in the case of a drug substance which acts directly and locally to produce the expected effect, it is likewise excreted without being utilized if the duration of contact is short. Particularly in cases in which the drug substance is sparingly soluble, its pharmacologic actions cannot be effectively utilized. Therefore, in the conventional drug delivery systems, it is difficult to insure absorption of active ingredients beyond a limited time period.
European Patent Publication No. 0368247A3 discloses a matrix preparation such that a pharmaceutically active ingredient is dispersed in a polyglycerol fatty acid ester-based matrix which is solid at ambient temperature. Moreover, European Patent Publication No. 406856A2 discloses an FGF protein composition which is a granulated preparation using a polyglycerol fatty acid ester. Furthermore, European Patent Publication No. 0455391 proposes a granulated preparation prepared by thermal fluidization of a particulate composition containing a granular polyglycerol fatty ester having a melting point of 40.degree. to 80.degree. C. and an active ingredient.
However, none of these prior art literature teach or suggest a pharmaceutical preparation having a gastrointestinal mucosa-adherent property.